Evaluating the optimal duration of medication treatment for opioid use disorder

Abstract

Background and aims: Clinicians have little guidance on the ideal length of time patients should remain on medication treatment for opioid use disorder (MOUD) before being able to safely discontinue MOUD. This study estimated how the risk of all-cause mortality changes with the duration of MOUD, controlling for patient characteristics that change the risk profile independent of duration of therapy. Design, setting and participants: Retrospective cohort study using electronic health record data from the US Veterans Healthcare Administration. Veterans initiating MOUD with buprenorphine, methadone or extended-release naltrexone from October 2010 to September 2020. Our analytic sample included 19 666 buprenorphine initiators, 8675 methadone initiators and 4007 extended-release naltrexone initiators. Measurement: Duration of MOUD was measured in days. Discontinuation was defined as a gap in any MOUD coverage exceeding 28 days, regardless of MOUD type initiated. The primary outcome was all-cause mortality. We estimated multistate survival models allowing for the modeling of multiple states (i.e. on and off MOUD, death) without having to consider censoring or competing events, while adjusting for sociodemographic, clinical, prescription and facility and provider characteristics. Findings: We observed approximately 226 000 person-years of time at risk for discontinuation or pre-discontinuation death, during which we observed 26 841 discontinuations (118.9 discontinuations per 1000 person-years). We similarly observed a total of about 106 000 person-years of post-discontinuation follow-up, during which we observed 3251 deaths (3.1 deaths per 1000 person-years). We found the largest marginal gain in probability of 6-year survival from an additional year on MOUD appears to occur around 2 years, as compared to 6 months on MOUD. Statistically significant gains continued through approximately 4–5 years of MOUD retention relative to 6-month MOUD retention. After 4–5 years, the marginal gain from one additional year of MOUD was not statistically significant. Conclusions: Among US veterans, the benefit of retention on medication treatment for opioid use disorder (MOUD) towards overall survival continues through at least 4 years of MOUD treatment. Quality metrics based on 6-month MOUD retention may be insufficient.